Noninvasive, nuclear imaging techniques can be used to obtain basic and diagnostic information about the physiology and biochemistry of a variety of living subjects including experimental animals, normal humans, and patients. These techniques rely on the use of sophisticated imaging instrumentation which is capable of detecting radiation emitted from radiotracers administered to such living subjects. The information obtained can be reconstructed to provide planar and tomographic images which reveal the distribution of the radiotracer as a function of time. Use of appropriately designed radiotracers can result in images which contain information on structure (low resolution), function, and most importantly, physiology and biochemistry of the subject. Much of this information cannot be obtained by any other means. The radiotracers used in these studies are designed to have defined behaviors in vivo which permit the determination of specific information concerning the physiology or biochemistry of the subject or of the effect that various diseases or drugs have on the physiology or biochemistry of the subject. Currently, radiotracers are available for obtaining useful information concerning such things as cardiac function, myocardial blood flow, lung perfusion, liver function, brain blood flow, regional brain glucose, and oxygen metabolism. A major effort has been made over the past 30 years to develop radiotracers to image the pancreas with little success (see Tothill, p., Heading, R.C., Shearman, D.J.C. In: Radiopharmaceuticals and Labelled Compounds, proceedings of a symposium, Copenhagen, March 1973, 1:26-30).
A variety of radiotracers have been proposed for pancreatic imaging including compounds labeled with either positron or gamma emitting nuclides. For imaging, the most commonly used positron emitting radiotracers are .sup.11 C, .sup.18 F, .sup.15 O, and .sup.13 N, all of which are accelerator produced, and have half-lives of 20, 110, 10, and 2 min respectively. Since the half-lives of these radionuclides are so short, it is only feasible to use them at institutions which have an accelerator on site for their production, limiting their use to approximately 25 medical centers in the U.S. and only about 50 throughout the world. Several gamma emitting radiotracers are available which can be used by essentially any hospital in the U.S. and in most hospitals throughout the world. The most widely used of these are .sup.99m Tc, .sup.201 T1, and .sup.123 I. .sup.201 T1 is a monovalent cation which is used for measuring myocardial blood flow. Both .sup.99m Tc and .sup.123 I can be incorporated into a variety of radiotracers and are widely used in most modern hospitals. .sup.99m Tc is generator produced, has a 6 hour half life, and emits a 140 keV gamma photon which makes this radionuclide photon emission computerized tomography (SPECT) cameras. .sup.99m Tc is a transition metal which forms a wide variety of complexes with molecules containing coordinating ligands (e.g. molecules with free thiol, amine, carboxyl functional groups). .sup.99m Tc labeled compounds have been developed for many diagnostic imaging applications, such as functional studies (e g. cardiac, renal, liver) and perfusion studies (myocardial, brain, lung). The design of these tracers is complicated and not relevant to the present invention.
.sup.123 I is also nearly ideal for use with planar and SPECT cameras. It is accelerator produced, has a 13 hour half-life, and emits a 159 keV gamma photon which is efficiently detected by both planar and SPECT cameras. The most important advantage .sup.123 I has as a radiotracer for imaging applications is its ability to form covalent bonds with carbon which, in many cases, are stable in vivo and which have well understood effects on physiochemical properties of small molecules.
In the past few years, one of the most active areas of nuclear medicine research has been in the development of receptor imaging radiotracers. These tracers bind with high affinity and specificity to selective hormone and neuroreceptors. Successful examples include radiotracers for imaging the following receptors: estrogen, muscarinic, dopamine D1 and D2, and opiate. These tracers are useful for obtaining information on receptor distribution and concentration as well as on regional blood flow. Most of this work has focused on positron emitting radiotracers. However, .sup.123 I has been used to label small molecules to yield several radiotracers useful for receptor imaging; successful examples include 3 iodoquinuclidinyl benzilate and iodo-dexetimide for muscarinic receptors, iodo estradiol for estrogen receptors, and (S)-3-([.sup.125 I]-iodo-N-[(1-ethyl-2-pyrrolidinyl)]methyl-2-hydroxy-6-methoxybenzamide for dopamine-D2 receptors.